NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine

NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine was administered by particle-mediated epidermal delivery (PMED) at a pressure of 500 psi using the XR-1 Powderject® delivery device. The 4 microgram dosage of NY-ESO-1 was administered as 4 X 1 microgram PMEDs in close proximity. Similarly, the 8 microgram dosage was administered as 8 X 1 microgram PMEDs. The third cohort of patients received the 8 microgram dosage as a cluster dosage of 4 doses (day 1, 3, 5, 8) as 2 X 1 microgram PMEDs per day.

Blood samples were to be obtained at baseline, 2 weeks after each vaccination, prior to the second and third vaccination, and 4 weeks after the third vaccination for the assessment of clinical hematology, biochemistry measurements and immunology responses. Patients were to be evaluated for toxicity throughout the study.

Delayed-type hypersensitivity (DTH) testing was to be performed at baseline and at the 2-week visit following the first and third vaccinations.

NY-ESO-1 and/or LAGE-1 specific antibodies were to be assessed in all patients by an enzyme-linked immunosorbent assay (ELISA). NY-ESO-1 specific CD4+ and CD8+ T-cells were to be assessed in all patients by tetramer and/or ELISPOT assays.

Disease status was to be assessed at baseline and 4 weeks after the third vaccination in patients with measurable disease.

Inclusion criteria

Patients were eligible for enrollment if they fulfilled all of the following criteria:

• Histologically proven tumor type known to express NY-ESO-1 or LAGE-1 (prostate cancer, breast cancer, bladder cancer, hepatocellular cancer, synovial sarcoma, leiomyosarcoma, head and neck, lung cancer, esophageal, ovarian, neuroblastoma); or NY-ESO-1 or LAGE-1 positive tumors determined by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis, preferably, or immunohistochemistry or expression of LAGE-1 by RT-PCR.
• Advanced disease and have declined, delayed, failed or completed standard therapy.
• Full recovery from surgery.
• Expected survival of at least 6 months.
• Karnofsky performance scale ≥ 60.
• Adequate bone marrow, kidney, liver and immune functions.
• Able and willing to give valid written informed consent.

Exclusion criteria

• Clinically significant heart disease (NYHA Class III or IV).
• Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders, clinically significant liver or renal insufficiency requiring treatment.
• Patients with serious intercurrent illness, requiring hospitalization.
• Known HIV, Hepatitis B or Hepatitis C positivity.
• History of autoimmune diseases (e.g. SLE, scleroderma). Vitiligo is not an exclusion criterion.
• Concomitant systemic treatment with corticosteroids, anti-histaminic drugs or non-steroidal anti-inflammatory drugs. Specific COX-2 inhibitors are permitted. Low dose aspirin is permitted. Topical or inhalational steroids are permitted.
• Evidence of skin disease (e.g. psoriasis, eczema or keloid formation) at the proposed administration site.
• Allergy to gold (including gold jewelry).
• History or evidence of chrysotherapy (gold salts).
• Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing (6 weeks for nitrosoureas).
• Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer, cervical carcinoma in situ.
• Mental impairment, in the opinion of the investigator, that may compromise the ability to give informed consent and comply with the requirements of the study.
• Lack of availability for immunological and clinical follow-up assessments.
• Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing.
• Pregnancy or breastfeeding.
• Women of childbearing potential: Refusal or inability to use effective means of contraception.